Pharmacokinetics and side effects of milrinone in infants and children after open heart surgery.
We investigated the pharmacokinetics and side effects of milrinone in infants and children (< or = 13 yr) after open heart surgery in this prospective, open-label study. Milrinone binding to cardiopulmonary bypass (CPB) circuitry was also examined in out two groups. Children in the small dose group (n = 11) received two 25-microg/kg boluses with a final infusion rate of 0.5 microg kg(-1) x min(-1); those in the large dose group (n = 8) received a 50-microg/kg bolus and a 25-microg/kg bolus with a final infusion rate of 0.75 microg x kg(-1) x min(-1). Blood samples for milrinone concentration were drawn 30 min after each bolus, at steady state, and after discontinuing the milrinone infusion. Pharmacokinetics were evaluated using traditional and nonlinear mixed effects modeling analysis. Milrinone kinetics best fit a two-compartment model. Steady-state plasma levels in the small and large dose groups were within the adult therapeutic range (113 +/- 39 and 206 +/- 74 ng/mL, respectively). The volumes of distribution (Vbeta) in infants (0.9 L/kg) and children (0.7 L/kg) were not different, but infants had significantly lower milrinone clearance (3.8 vs 5.9 mL x kg(-1) x min(-1)). Thrombocytopenia (defined as platelet count < or = 100,000 mm(-3)) occurred in 58%, and the risk increased significantly with duration of infusion. Tachyarrythmias were noted in two patients. Milrinone did not bind to CPB circuitry. We conclude that milrinone is cleared more rapidly in children than in adults. The major complication was thrombocytopenia.


CONCLUSIONS
Most pediatric dosing is based on data published for adults. Infants and children have kinetics that differ from adults. We studied the distribution of I.V. milrinone in infants and children after open heart surgery. Milrinone had a larger volume of distribution and a faster clearance in infants and children than in adults, and dosing should be adjusted accordingly.
Ramamoorthy
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Department of Anesthesiology, University of Washington School of Medicine, Seattle, USA. chandra@u.washington.edu
Anderson
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Williams
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Lynn
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D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002315:Cardiopulmonary Bypass / Q000295:instrumentation; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008657:Metabolic Clearance Rate; D020105:Milrinone; D010976:Platelet Count / Q000187:drug effects; D011446:Prospective Studies; D011728:Pyridones / Q000009:adverse effects / Q000493:pharmacokinetics*; D012044:Regression Analysis; D019616:Thoracic Surgical Procedures
D011728:Pyridones; D020105:Milrinone